|
Growth Hormone
Increased energy, improved stamina, more optimistic attitude,Growth
hormone, also known as somatotropin, is a protein hormone of 191 amino
acids that is synthesized and secreted by cells called somatotrophs in
the anterior pituitary. It is a major participant in control of several
complex physiologic processes, including growth and metabolism.
Growth hormone is also of considerable interest as a drug used in both
humans and animals.
Physiologic
Effects of Growth Hormone
 A
critical concept in understanding growth hormone activity is that it
has two distinct types of effects:
Direct effects are the result of growth hormone binding its receptor on
target cells. Fat cells (adipocytes), for example, have growth hormone
receptors, and growth hormone stimulates them to break down
triglyceride and supresses their ability to take up and accumulate
circulating lipids.
Indirect
effects are mediated primarily by a
insulin-like growth factor-1 (IGF-1), a hormone that is secreted from
the liver and other tissues in response to growth hormone. A majority
of the growth promoting effects of growth hormone is actually due to
IGF-1 acting on its target cells.
Keeping this distinction in mind, we can discuss two major roles of growth hormone and its minion IGF-1 in physiology.
Effects
on Growth
Growth is a
very complex process, and requires the coordinated action of several hormones. The major role of
growth hormone in stimulating body growth is to stimulate the liver and
other tissues to secrete IGF-1. IGF-1 stimulates proliferation of
chondrocytes (cartilage cells), resulting in bone growth. Growth
hormone does seem to have a direct effect on bone growth in stimulating
differentiation of chondrocytes.
IGF-1
also
appears to be the key player in muscle growth. It stimulates both the
differentiation and proliferation of myoblasts. It also stimulates
amino acid uptake and protein
synthesis in muscle and other tissues.
Metabolic
Effects
Growth hormone
has important effects on protein, lipid and carbohydrate metabolism. In some cases, a direct
effect of growth hormone has been clearly demonstrated, in others,
IGF-1 is thought to be the critical mediator, and some cases it appears
that both direct and indirect effects are at play.
Protein
metabolism: In general, growth hormone stimulates protein
anabolism in many tissues. This effect reflects increased amino acid
uptake, increased protein synthesis and decreased oxidation of proteins.
Fat
metabolism: Growth hormone enhances the utilization of fat
by stimulating triglyceride breakdown and oxidation in adipocytes.
Carbohydrate
metabolism: Growth hormone is one of a battery of hormones
that serves to maintain blood glucose within a normal range. Growth
hormone is often said to have anti-insulin activity, because it
supresses the abilities of insulin to stimulate uptake of glucose in
peripheral tissues and enhance glucose synthesis in the liver. Somewhat
paradoxically, administration of growth hormone stimulates insulin
secretion, leading to hyperinsulinemia.
Control
of Growth Hormone Secretion
Production of
growth hormone is modulated by
many factors, including stress, exercise, nutrition, sleep and growth
hormone itself. However, its primary controllers are two hypothalamic
hormones and one hormone from the stomach:
· Growth
hormone-releasing hormone (GHRH) is a hypothalamic peptide that stimulates both the synthesis and secretion of growth hormone.
· Somatostatin
(SS) is a peptide produced by several tissues in the body, including the hypothalamus. Somatostatin
inhibits growth hormone release in response to GHRH and to other stimulatory factors such as low blood glucose concentration.
· Ghrelin is a peptide hormone secreted from
the stomach. Ghrelin binds to receptors on somatotrophs and potently
stimulates secretion of growth hormone.
Growth hormone
secretion is also part of a negative feedback loop involving IGF-1.
High blood levels of IGF-1 lead to decreased secretion of growth
hormone not only by directly suppressing the somatotroph, but by
stimulating release of somatostatin from the hypothalamus.
Growth hormone also feeds back to inhibit GHRH secretion and probably
has a direct (autocrine) inhibitory effect on secretion from the
somatotroph.
Integration of all the factors that affect growth hormone synthesis and
secretion lead to a pulsatile pattern of release.
Basal concentrations of growth hormone in blood are very low. In
children and young adults, the most intense period of growth hormone
release is shortly after the onset of deep sleep.
Disease
States
States of both
growth hormone deficiency and excess provide very visible testaments to the role of this hormone in
normal physiology.
Such disorders can reflect lesions in either the hypothalamus, the
pituitary or in target cells. A deficiency state can result not only
from a deficiency in production of the hormone, but in the target
cell's response to the hormone. (for more information about deficiency
see decline)
Pharmaceutical and Biotechnological Uses of Growth Hormone
In years past,
growth hormone purified from human cadaver pituitaries was used to treat children with severe growth
retardation. More recently, the virtually unlimited supply of
recombinant growth hormone has lead to several other applications to
human and animal populations.
The role of growth hormone in normal aging and some of the cosmetic
symptoms of aging appear to be amenable to growth hormone therapy. This
still is an active area of research, and additional information and
recommendations about risks and benefits will undoubtedly surface in
the near future.
Growth
Hormone and Aging
Normal Changes
in the Growth Hormone Axis with Aging
The rate of GH
secretion from the anterior
pituitary is highest around puberty, and declines progressively
thereafter. This age-related decline in GH secretion involves a number
of changes in the GH axis, including decreased serum levels of
insulin-like growth factor-1 (IGF-1) and decreased secretion of growth
hormone-releasing hormone from the hypothalamus. The cause of the
normal age-related decrease in GH secretion is not well understood, but
is thought to result, in part, from increased secretion of
somatostatin, the GH-inhibiting hormone.
Normal aging
is accompanied by a number of
catabolic effects, including:
a decrease
in lean mass,
increase in fat mass, and
decrease in bone density.
Associated
with these physiologic changes is
a clinical picture often referred to as the somatopause:
frailty,
muscle atrophy,
relative obesity,
increased frequency of fractures and
disordered sleep.
These clinical
signs of aging are, doubtless, the manifestation of a very complex set of changes which
involve, at least in part, the GH-axis.Naturally, this has spurred
considerable interest in administering supplemental GH as a "treatment"
for aging in humans, and the availability of recombinant human GH has
made such studies feasible. | 
